Kaplan + Sadock's Synopsis of Psychiatry, 11e

Psychopharmacological Treatment 29

second- or third-generation antidepressants. More recently, older agents used as treatments for psychosis became known as typical, conventional, or traditional neuroleptics. Newer ones became atypical neuroleptics. In order to eliminate much of this confusion, in this section, drugs are presented according to shared mechanism of action or by similarity of structure to provide consistency, ease of reference, and comprehensiveness. Pharmacological Actions Both genetic and environmental factors influence individual response to, and tolerability of, psychotropic agents. Thus, a drug that may not prove effective in many patients with a dis- order can dramatically improve symptoms in others. In these cases, identification of characteristics that might predict poten- tial candidates for that drug becomes important, but often remains elusive. Drugs, even within the same class, are distinguished from one another by often subtle differences in molecular structure, types of interactions with neurotransmitter systems, differences in pharmacokinetics, the presence or absence of active metabo- lites, and protein binding. These differences, combined with the biochemistry of the patient, account for the profile of efficacy, tolerability, and safety and the risk-to-benefit ratio for the indi- vidual. These multiple variables, some poorly understood, make it difficult to predict a drug’s effect with certainty. Nevertheless, knowledge of the nature of each property increases the likeli- hood of successful treatment. The clinical effects of drugs are best understood in terms of pharmacokinetics, which describes what the body does to a drug, and pharmacodynamics, which describes what the drug does to the body. Pharmacokinetics and pharmacodynamics need to be seen in the context of the underlying variability among patients with respect to how drug effects are expressed clinically. Patients dif- fer in their therapeutic response to a drug and the experience of side effects. It is increasingly clear that these differences have a strong genetic basis. Pharmacogenetics research is attempting to identify the role of genetics in drug response. Drug Selection Although all U.S. Food and Drug Administration (FDA)- approved psychotropics are similar in overall effectiveness for their indicated disorder, they differ considerably in their phar- macology and in their efficacy and adverse effects on individual patients. The ability of a drug to prove effective, thus, is only partially predictable and is dependent on poorly understood

▲▲ 29.1 General Principles of Psychopharmacology Psychopharmacologic advances continue to dramatically expand the parameters of psychiatric treatments. Greater under- standing of how the brain functions has led to more effective, less toxic, better-tolerated, and more specifically targeted thera- peutic agents. With the ever-increasing sophistication and array of treatment options, clinicians, however, must remain aware of potential adverse effects, drug–drug (and drug–food or drug– supplement) interactions, and how to manage the emergence of unwanted or unintended consequences. Newer drugs could ulti- mately lead to side effects that are not recognized initially. Keep- ing up with the latest research findings is increasingly important as these findings proliferate. A thorough understanding of the management of medication-induced side effects (either through treating the effect with another agent or substituting another pri- mary agent) is necessary. Classification Medications used to treat psychiatric disorders are referred to as psychotropic drugs. These drugs are commonly described by their major clinical application, for example, antidepressants, antipsychotics, mood stabilizers, anxiolytics, hypnotics, cogni- tive enhancers, and stimulants. A problem with this approach is that, in many instances, drugs have multiple indications. For example, drugs such as the selective serotonin reuptake inhibi- tors (SSRIs) are both antidepressants and anxiolytics, and the serotonin-dopamine antagonists (SDAs) are both antipsychotics and mood stabilizers. Psychotropic drugs have also been organized according to structure (e.g., tricyclic), mechanism (e.g., monoamine oxidase inhibitor [MAOI]), history (e.g., first generation, traditional), uniqueness (e.g., atypical), or indication (e.g., antidepressant). A further problem is that many drugs used to treat medical and neurological conditions are routinely used to treat psychiatric disorders. In addition, psychotropic drug terminology can be confus- ing. The first pharmaceutical agents used to treat schizophre- nia were termed tranquilizers. When newer drugs emerged as therapies for anxiety, a distinction was drawn between major and minor tranquilizers. At first, antidepressants were tricyclic antidepressants (TCAs) or MAOIs. In the 1970s and 1980s, as newer antidepressant drugs emerged, they were labeled as

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